1-(2,4-diamino-pyrimidin-5-yl)-1-(3,4,5-trimethoxy-phenyl)-ethanol | 77476-72-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-(2,4-diamino-pyrimidin-5-yl)-1-(3,4,5-trimethoxy-phenyl)-ethanol
• 英文别名: 2,4-Diamino-α-methyl-α-(3,4,5-trimethoxyphenyl)-5-pyrimidin-methanol；1-(2,4-Diaminopyrimidin-5-yl)-1-(3,4,5-trimethoxyphenyl)ethanol
• CAS: 77476-72-3
• 化学式: C₁₅H₂₀N₄O₄
• 分子量: 320.348
• InChiKey: IUOBEQAECXKQPZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  126
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-(2,4-diamino-pyrimidin-5-yl)-1-(3,4,5-trimethoxy-phenyl)-ethanol 在 palladium on activated charcoal 氢气 、 溶剂黄146 、 三氟乙酸 作用下， 生成 5-[1-(3,4,5-trimethoxy-phenyl)-ethyl]-pyrimidine-2,4-diamine
  参考文献：
  名称：

  Analysis of complexes of inhibitors with Cryptosporidium hominis DHFR leads to a new trimethoprim derivative

  摘要：

  Cryptosporidiosis, an opportunistic infection affecting immunocompromised patients, the elderly, and children, is still an untreatable disease since the causative agent, Cryptosporidium hominis, is essentially resistant to all clinically used antimicrobial agents. In order to accelerate the design of new potent and selective inhibitors targeting dihydrofolate reductase of C. hominis (ChDHFR), we determined the structural basis for the potency of existing DHFR inhibitors using superpositions of the structure of ChDHFR with other species and analysis of active site complexes of ChDHFR bound to ligands exhibiting a wide range of IC50 values. This information was used to develop an accurate docking model capable of identifying potent inhibitors in silico. A series of C7-trimethoprim derivatives, designed to exploit a unique pocket in ChDHFR, was synthesized and evaluated; 7-ethyl TMP has four times higher activity than TMP against ChDHFR. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.05.047
• 作为产物：
  描述：

  甲氧苄啶 在 manganese(IV) oxide 作用下， 生成 1-(2,4-diamino-pyrimidin-5-yl)-1-(3,4,5-trimethoxy-phenyl)-ethanol
  参考文献：
  名称：

  Analysis of complexes of inhibitors with Cryptosporidium hominis DHFR leads to a new trimethoprim derivative

  摘要：

  Cryptosporidiosis, an opportunistic infection affecting immunocompromised patients, the elderly, and children, is still an untreatable disease since the causative agent, Cryptosporidium hominis, is essentially resistant to all clinically used antimicrobial agents. In order to accelerate the design of new potent and selective inhibitors targeting dihydrofolate reductase of C. hominis (ChDHFR), we determined the structural basis for the potency of existing DHFR inhibitors using superpositions of the structure of ChDHFR with other species and analysis of active site complexes of ChDHFR bound to ligands exhibiting a wide range of IC50 values. This information was used to develop an accurate docking model capable of identifying potent inhibitors in silico. A series of C7-trimethoprim derivatives, designed to exploit a unique pocket in ChDHFR, was synthesized and evaluated; 7-ethyl TMP has four times higher activity than TMP against ChDHFR. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.05.047

文献信息

• Analysis of complexes of inhibitors with Cryptosporidium hominis DHFR leads to a new trimethoprim derivative
  作者：Veljko M. Popov、David C.M. Chan、Yale A. Fillingham、W. Atom Yee、Dennis L. Wright、Amy C. Anderson

  DOI：10.1016/j.bmcl.2006.05.047

  日期：2006.8

  Cryptosporidiosis, an opportunistic infection affecting immunocompromised patients, the elderly, and children, is still an untreatable disease since the causative agent, Cryptosporidium hominis, is essentially resistant to all clinically used antimicrobial agents. In order to accelerate the design of new potent and selective inhibitors targeting dihydrofolate reductase of C. hominis (ChDHFR), we determined the structural basis for the potency of existing DHFR inhibitors using superpositions of the structure of ChDHFR with other species and analysis of active site complexes of ChDHFR bound to ligands exhibiting a wide range of IC50 values. This information was used to develop an accurate docking model capable of identifying potent inhibitors in silico. A series of C7-trimethoprim derivatives, designed to exploit a unique pocket in ChDHFR, was synthesized and evaluated; 7-ethyl TMP has four times higher activity than TMP against ChDHFR. (c) 2006 Elsevier Ltd. All rights reserved.